Loosening of orthopaedic implants is a significant problem that leads to pain, loss of function, and, ultimately, revision surgery. Since one important cause of aseptic loosening appears to arise from wear debris-induced osteolysis, an understanding of the mechanisms involved in this process is crucial to develop new methods to prevent implant loosening. A variety of studies suggest that wear particles induce osteolysis. These include histological examination of tissue surrounding revised implants, characterization of the wear particles found in such tissues, and measurement of bone resorptive cytokines produced in response to the particles. However, cytokines that inhibit bone resorption are also likely produced. Thus, it is not possible to predict, a priori, whether the mixture of factors produced in response to wear particles is likely to have a net stimulatory or inhibitory effect on bone resorption. It is hypothesized that specific cellular interactions and cytokines are functionally important in stimulation of bone resorption by wear particles. This application focuses on documenting these important processes. Particle composition, size, shape, and surface chemistry likely regulate the effect of such particles on bone resorption. Thus, particles of a variety of different compositions will be examined. The application's Specific Aims are therefore: 1) to assess the effects of orthopaedic wear debris on bone resorption; 2) to determine the cytokines involved in stimulation of bone resorption by orthopaedic wear debris; and 3) to determine the cell types involved in stimulation of bone resorption by orthopaedic wear debris.